Cancer is characterized primarily by an increase in the number of abnormal cells derived from a given normal tissue, invasion of adjacent tissues by these abnormal cells, or lymphatic or blood-borne spread of malignant cells to regional lymph nodes and to distant sites (metastasis). Clinical data and molecular biologic studies indicate that cancer is a multistep process that begins with minor preneoplastic changes, which may under certain conditions progress to neoplasia. The neoplastic lesion may evolve clonally and develop an increasing capacity for invasion, growth, metastasis, and heterogeneity, especially under conditions in which the neoplastic cells escape the host's immune surveillance (Roitt, I., Brostoff, J and Kale, D., Immunology, 17.1-17.12 (3rd ed., Mosby, St. Louis, Mo., 1993)).
Cancers figure among the leading causes of death worldwide, accounting for 8.2 million deaths in 2012. It is expected that annual cancer cases will rise from 14 million in 2012 to 22 million within the next two decades (See Cancer Fact sheet No. 297, World Health Organization, February 2014, retrieved 10 June 2014 and Globocan 2012, IARC).
Certain aminopurine compounds have been reported to show pharmaceutical properties suitable for clinical development in the treatment of cancer. Aminopurine compounds can be made using conventional organic syntheses and commercially available starting materials. By way of example and not limitation, aminopurine compounds can be prepared as described in U.S. Pat. Nos. 7,723,340, 8,158,635, and U.S. patent application Ser. No. 14/874,513.
One example of an aminopurine compound with therapeutic potential is cis-4-[2-{[(3 S,4R)-3-fluorooxan-4-yl]amino}-8-(2,4,6-trichloroanilino)-9H-purin-9-yl]-1-methylcyclohexane-1-carboxamide, alternatively named (1s,4s)-4-(2-(((3S,4R)-3-fluorotetrahydro-2H-pyran-4-yl)amino)-8-((2,4,6-trichlorophenyl)amino)-9H-purin-9-yl)-1-methylcyclohexane-1-carboxamide. The compound and a process of synthesizing the compound are described in U.S. Pat. No. 9,512,124, which is incorporated herein by reference in its entirety.
Despite its current availability, a need still exists for the development of alternative synthetic processes for preparing (1s,4s)-4-(2-(((3S,4R)-3-fluorotetrahydro-2H-pyran-4-yl)amino)-8-((2,4,6-trichlorophenyl)amino)-9H-purin-9-yl)-1-methylcyclohexane-1-carboxamide useful for multi-kg production of the compound.